PROJECT ABSTRACT AOM is the most common reason for antimicrobial prescribing in US children, and due to the high prevalence of disease and frequent recurrences is believed to be partially responsible for the ongoing increase in antibiotic resistance among pathogenic bacteria. Local, sustained delivery of active therapeutics directly to the middle ear for the treatment of OM could potentially allow for much higher middle ear drug concentrations than from systemic administration, which could allow for a faster and more complete eradication of OM bacteria, while minimizing systemic exposure and its adverse effects, particularly selection of drug-resistant bacteria. We have recently described a hydrogel containing antibiotics and chemical permeation enhancers that was capable of enhancing antibiotic flux across the tympanic membrane, to produce a sufficient flux of antibiotic across the tympanic membrane (TM) from a single application to be able to treat OM. We have subsequently optimized this formulation in terms of gelation properties and adherence to the eardrum, and shown efficacy in a model of otitis media. We hypothesize that these formulations will also be able to prevent OM, and mitigate biofilm formation in the middle ear. Here we propose a research plan that will help in translating that proof-of-concept toward a clinical reality. Toward that end, we have assembled a multidisciplinary and multi-institutional collaboration with a proven track record of working together.